The invention relates to chloro-, hydroxy- and alkoxysilane derivatives of polysaccharides or oligosaccharides as novel compounds which are polymerizable and cross-linkable, and a method for obtaining them.
The invention also relates to novel material supports obtained from said derivatives and containing said silane derivatives of polysaccharides or oligosaccharides chemically grafted by a covalent bond with the support and polymerizable and cross-linkable in a three-dimensional network. The invention also relates to a method for obtaining said support materials.
The invention also relates to the use of said support materials in separation or in preparation of enantiomers, through employment in gaseous, liquid or supercritical chromatography, by electrophoresis, electrochromatography or by percolation processes through membranes containing said support materials.
The separation of enantiomers has been an expanding field for some twenty years, at both the preparation and analysis level. This is true in particular of pharmacy applications, where legislation requires a separate study of the optical isomers of any compound included in the composition of a medicament. Substituted polysaccharides have been the subject of numerous studies, and celluloses deposited physically on a silica gel support are marketed. However, such compounds have the disadvantage of being most often soluble in organic polar solvents, which singularly limits their use.
Recent solutions have been provided to the problem of solubilization, by establishing covalent bonds between the substituted polysaccharide and the support. Kimata et al. published their results (Analytical Methods and Instrumentation, Vol. 1, 23-29 (1993)) on a chiral stationary phase based on cellulose-tris-2,3,6-(4-vinyl benzoate) deposited on silica gel then polymerized on the support.
The chromatographic data obtained with two racemic test mixtures are as follows:
where
kxe2x80x21 and kxe2x80x22 are the capacity factors, that is to say if i=1 or 2, kxe2x80x2i=(tRi-to/to, tRi being the retention time of the compound i and to the dead time;
xcex1 is the selectivity factor: xcex1=(tR2-to)/(tR1-to)=kxe2x80x22/kxe2x80x21             R      s        ⁢          xe2x80x83        ⁢    is    ⁢          xe2x80x83        ⁢    the    ⁢          xe2x80x83        ⁢    resolution    ⁢          xe2x80x83        ⁢          factor      :              R        s              =      -                                        1            ⁢                          (                              α                -                1                            )                        ⁢                          (                                                k                  xe2x80x2                                ⁢                2                            )                                                                                      (              -              )                        ⁢                          (              -              )                        ⁢                                          (                N                )                                            1                /                2                                                                                      4            ⁢                          (              α              )                        ⁢                          (                              1                +                                                      k                    xe2x80x2                                    ⁢                  2                                            )                                          
N being the number of plates determined on the basis of chromatographic values measured on chromatogram.
A systematic decline in the obtained selectivity factors can be seen between the deposited support and the deposited and polymerized support: 10% less on trans-stilbene oxide (xcex1changes from 1.54 to 1.39) and 7.5% less for 1-(1-naphthyl)ethanol (xcex1 changes from 1.32 to 1.22).
This phenomenon could be explained by a partial solubility of the polymerized support because of an incomplete polymerization due to a low reactivity of the vinyl benzoate group in the reaction conditions employed.
On the other hand, Kimata et al. offer no example of separation in a pure polar solvent (patent or publication).
Okamoto et al. have described (EP-B-0 155 637) polymers chemically bound to silica gel. They describe in particular the grafting of cellulose tris-2,3,6-phenyl carbamate onto silica gel via a tritylated intermediate then the realization of the covalent bond, between the silica gel and the partially derived polysaccharide carbamate, by action of a diisocyanate.
The results of the elemental analyses carried out at various synthesis stages are as follows (EP-B-0 155 637, page 8 to page 9, line 33).
The drop in the rate of grafting between the cellulose deposited on silica (2) and the cellulose phenyl carbamate bound to the silica (4) is substantial knowing that the rate of (4) calculated according to (2) is of the order of 14% carbon. The loss of hydrocarbon groups can thus be estimated at 80% from the realization of the covalent bond, between the cellulose and the silica, by the diisocyanate arm followed by the derivation of the OHs with phenyl isocyanate and the final washing with chloroform. No example of separation in polar solvents is given for the support obtained.
Okamoto et al. have described (JP-A-06-206 893) an oligosaccharide chemically bound to silica gel via an amine-reduced imine function. The amylose is then regenerated by the chemoenzymatic route from this oligosaccharide. The available hydroxyl functions are then derived as carbamate functions. No example of separation in a pure polar solvent is given.
On the other hand, it is beneficial to work with a substantial column overload for preparatory applications. The possibility of using 100% of the chiral material in the form of balls of pure polymer of substituted polysaccharides, instead of depositing them physically on a support, has proved effective in increasing the mass yields of preparatory chiral chromatography processes. Thus patents EP-B-348 352, and EP-B-316 270 and WO-A-96/27 639 relate to the realization of cellulose balls for the separation of optical isomers.
However, the pure polymer balls are soluble in polar solvents such as halogenated solvents, tetrahydrofuran, dioxan, etc. It is thus impossible to use these pure solvents or mixtures with high proportions of the latter to realize separations of isomers.
In order to overcome this drawback, Francotte et al. described the polymerization by radiation of derived polysaccharides (WO-A-96/27 615).
However, the rate of polymerization seems difficult to control in such a process, cross-linking by photochemical process preferentially occurring at the surface of the polymer ball, the rays being unable to penetrate inside the ball. No example of separation is given in a pure polymer.
Francotte et al. have also described in international application WO-A-97/04 011 the chemical cross-linking of carbamates and esters of polysaccharides not containing a polymerizable group. According to the author, crosslinking took place in the presence of a radical polymerization initiator. The reaction mechanism and the structure of the products obtained are not described. No example of separation in a pure polar solvent is given.
Lange at al. have described (U.S. Pat. No. 5,274,167) the polymerization of optically active derivatives of methacrylic acid, the structure of the support not being explained. No example of separation in a pure polar solvent is given.
Minguillon et al. have described the synthesis of partially derived cellulose carbamates with an undecenoyl chloride. However, the structure of the support is not explained (J. of Chromatog. A 728 (1996), 407-414 and 415-422).
Oliveros et al. (WO-A-95/18 833) describe polysaccharide derivatives containing an ethylene radical and deposited on a silica gel support containing vinyl groups then polymerized. No example of separation is given with a pure polar solvent.
The present invention relates to the preparation of novel silane derivatives of polysaccharides or oligosaccharides containing chlorosilane, hydroxysilane or alkoxysilane functions which are easily polymerizable and cross-linkable in a three-dimensional network. Said derivatives are used for obtaining novel support materials containing them and characterized in that that are bound by a chemical covalent bond to the support and concomitantly polymerized and cross-linked in a three-dimensional network. Said support materials are used for the separation of enantiomers by chromatography, in particular in pure polar solvents such as chloroform, dichloromethane, tetrahydrofuran, acetone, toluene, ethyl acetate or any other polar organic solvent.
The present invention also relates to a method for obtaining silane derivatives of polysaccharides or oligosaccharides containing chlorosilane, hydroxysilane or alkoxysilane groups. The subsequent obtaining of support materials is realized by physically depositing said silane derivatives of polysaccharides obtained, on a support and reacting the chlorosilane, hydroxysilane or alkoxysilane functions with said support in order to realize chemical covalent bonds of xe2x80x94Sixe2x80x94Oxe2x80x94(support) type with polymerization and concomitant three-dimensional cross-linking of the silane derivative of polysaccharide by creation of chemical covalent bonds of xe2x80x94Sixe2x80x94Oxe2x80x94Sixe2x80x94 type between the chains of the polysaccharide derivative. The method also includes the separation and preparation of enantiomers by employing said support materials in liquid, gas or supercritical chromatography processes, in organic synthesis or in percolation processes through membranes containing said support materials.
The support materials according to the invention possess a stability and total insolubility in polar solvents such as tetrahydrofuran, chloroform, dichloromethane, acetonitrile, toluene or ethyl acetate, as well as in any other organic solvent such as ethers for example. The stability and insolubility of said support materials is effective up to high temperature (greater than 100xc2x0 C.).
The chlorosilane, hydroxysilane or alkoxysilane derivatives of polysaccharides according to the invention are constituted by linkages of osidic chiral units forming linear, branched or cyclic chains and which can be represented by one of the general formulae below: 
in which:
a) the symbols X1, X2 and X3, identical or different, each represent an oxygen atom or the xe2x80x94NH group;
b) each of the symbols R1, R2 and R3 independently represents:
a chlorosilane, hydroxysilane or alkoxysilane radical of general formula [(X)3Sixe2x80x94Wxe2x80x94CH2xe2x80x94CH2]mAxe2x80x94Yxe2x80x94 (II) in which m is a non-zero integer at most equal to 5; Y is a single bond, an xe2x80x94NHxe2x80x94COxe2x80x94 group, an xe2x80x94NHxe2x80x94CSxe2x80x94 group or a xe2x80x94COxe2x80x94 group; A represents: (i) arylene radicals having 6 to 18 carbon atoms, optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms, alkyl radicals containing from 1 to 4 carbon atoms, alkoxy radicals containing from 1 to 4 carbon atoms, and nitro groups; ii) arylene radicals having at least 2 aromatic rings linked by a divalent atom or group, examples of such linking moieties including but not limited to xe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94, and polymethylene groups; specific examples include but are not limited to 4-phenoxy phenyl; c) aralkylene radicals having 7 to 40 carbon atoms, an example thereof including but not limited to 2,2-diphenyl 1,3-propylene; d) alkylene-aryl radicals, optionally containing divalent heteroatoms or groups, non-limiting examples being an oxygen atomxe2x80x94in the alkylene segment, specific examples including but not limited to 4-(xcfx89-undecenyloxy) phenyl. All other xcfx89-alkenenyl phenyl or xcfx89-alkenenyloxy phenyl radicals having up to e.g., 14 carbon atoms and non-limiting subgeneral of the alkylene-aryl radicals, W represents a single bond or the xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94Sxe2x80x94 group and X represents a halogen, a hydroxyl or an alkoxy;
or a radical having the formula A2xe2x80x94A1xe2x80x94CX4xe2x80x94 (III) in which X4 represents an oxygen or sulphur atom, A1 represents a single bond or an xe2x80x94NHxe2x80x94 group and A2 represents an aryl radical having from 6 to 24 carbon atoms, an aralkyl radical having from 7 to 36 carbon atoms or an alkylaryl radical having from 7 to 18 carbon atoms;
or a hydrogen atom or an NO2 group;
n being an integer between 5 and 20 000,
it being understood that, in each osidic chiral unit (Ia) to (Ik), at least one of the symbols X1, X2 and X3 represents an oxygen atom, and that, in at least part of the osidic units constituting the polysaccharide derivative, at least one of the symbols R1, R2 and R3 represents a radical of general formula (II) and at least one of the symbols R1, R2 and R3 represents a radical of general formula (III).
The arylene or aryl radicals contained respectively in the radicals of general formulae (II) and (III) may optionally be substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms, alkyl radicals containing from 1 to 4 carbon atoms, alkoxy radicals containing from 1 to 4 carbon atoms and nitro groups. The arylene radicals contained in the radicals of general formula (II) are, preferably, phenylene radicals or naphthylene radicals, optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms and alkyl radicals containing from 1 to 4 carbon atoms, alkoxy radicals containing from 1 to 4 carbon atoms and nitro groups. The aryl radicals contained in the radicals of general formulae II and (III) are, preferably, phenyl radicals or naphthyl radicals, optionally substituted by one or more atoms or radicals, identical or different, chosen from halogen atoms, alkyl radicals containing from 1 to 4 carbon atoms, alkyloxy radicals containing from 1 to 4 carbon atoms and nitro groups.
Generally, the silane derivatives of polysaccharides according to the invention have a degree of polymerization between 5 and 20 000 and preferably between 10 and 500.
Generally, the silane derivatives of polysaccharides according to the invention contain from 0.05 to 3, preferably from 0.05 to 2.95 groups of general formula (II) per structural unit of general formula (Ia) to (Ik), and from 0 to 2.95, preferably from 0.05 to 2.95 groups of general formula (III) per structural unit of general formula (Ia) to (Ik). Generally, the polysaccharide derivatives according to the invention derive from amylose, cellulose, chitosan xcex1, xcex2 or xcex3 cyclodextrins and dextran.
According to the invention, the silane derivatives of polysaccharides can be obtained by synthesis in two or three stages, where a reaction is carried out successively on a polysaccharide:
in stage 1, of a compound of general formula:
(CH2xe2x95x90CH)mAxe2x80x94Y1 xe2x80x83xe2x80x83(IV) 
in which R, m and A are defined as previously and Y1 represents a halogen atom (chlorine, bromine), an xe2x80x94Nxe2x95x90Cxe2x95x90O group or xe2x80x94Nxe2x95x90Cxe2x95x90S group or a xe2x80x94COxe2x80x94Zxe2x80x94 group in which Z represents a halogen atom (chlorine, bromine) in order to introduce an ethylene radical, subsequently modified in stage 3 into chlorosilane, hydroxysilane or alkoxysilane;
in an optional stage 2, an isocyanate or an isothiocyanate of general formula:
A2xe2x80x94A1xe2x80x94Nxe2x95x90Cxe2x95x90X5 xe2x80x83xe2x80x83(V) 
in which A2 and A1 are defined as previously and X, represents an oxygen or sulphur atom
or a compound of general formula:
A2xe2x80x94A1xe2x80x94COxe2x80x94Z1 xe2x80x83xe2x80x83(VI) 
in which A2 and A1 are defined as previously and Z1 represents a halogen atom (chlorine, bromine) in order to introduce a radical of general formula (III);
and, in stage 3, a compound of general formula: 
in which X is defined as previously in order to introduce a compound of general formula (II).
According to the invention, the introduction of the radicals of general formula (II) and optionally (III) takes place under the conditions customarily used for preparing an ether, an ester, an amide, a carbamate, a thiocarbamate, a urea or a thiourea, starting from the corresponding alcohol or amine.
Stage 1 and stage 2 are generally implemented in an organic solvent with a high boiling point, such as toluene, in the presence of an organic base such as pyridine or triethylamine. In the case where the compound of formula (IV) or (V) is an isocyanate, it is generally preferable to use a catalyst to encourage the kinetics of the reaction, dibutyltin dilaurate being preferred.
Obtaining the radicals of general formula (II) in stage 3 requires the reaction of compounds of formulae (VII) and (VIII) on the ethylene double bonds of the polysaccharides modified in stage 1 by the compounds of general formula (IV).
In stage 3, a distinction should be drawn in the procedure implemented as to whether a compound of formula (VII) or (VIII) is reacted.
In the first case a compound of formula (VII) is reacted.
The anti-Markovnikov addition reaction of thiol functions on ethylene double bonds, in the presence of a free radical initiator, which leads to the formation of thioether bonds is known per se. For example, Rosini and colleagues described the immobilization of cinchona alkaloids via a thioether bond in Tetrahedron Lett. 26, 3361-3364, 1985. More recently, Tambute and colleagues described the immobilization of tyrosine derivatives using the same technique in New J. Chem. 13 625-637, 1989. Even more recently, Caude and colleagues published the results of their work and showed the advantage of a covalent thioether bond in terms of chemical stability in J. Chromatogr. 550, 357-382,1991.
Among the compounds of formula (VIII) the generally preferred product is the compound of formula:
(CH3O)3Sixe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94SH 
or xcex3-mercaptopropyltrimethoxysilane, which is available commercially.
This compound is used in the presence of compounds obtained after realization of stages 1 and 2 or stage 1, in an organic solvent, the preferred organic solvents being toluene, tetrahydrofuran and chloroform. A free radical initiator is added to the reaction medium, such as benzoyl peroxide for example.
In a second case a compound of formula (VIII) is reacted in stage 3.
The hydrosilylation of ethylene double bonds by hydrogenosilanes is known per se and used to create silicon-carbon bonds. For example, Stuurman, H. W., in Chromatopgraphia, Vol. 25, no. 4, April 1988, pp. 265 to 271, has described the separation of enantiomers through the use of a stationary phase based on hydrosilylated quinine bound to silica gel by a covalent bond.
Among the compounds of formula (VIII) the two products which are generally preferred are the compounds of formula (C2H Q) 3SiH (triethoxysilane) and Cl3SiH (trichlorosilane), which are available commercially.
The triethoxysilane or trichlorosilane is used in the presence of compounds obtained after the realization of stages 1 and 2, or stage 1, in an organic solvent, the preferred solvents being toluene, dioxan or chloroform. A metal complex is generally used as catalyst. The preferred metal complexes are based on rhodium or platinum, such as hexachloroplatinic acid.
The invention also relates to support materials containing silane derivatives of polysaccharides of general formulae (1a) to (1k) and the chlorosilanes, hydroxysilanes and alkoxysilanes of which contained in the radicals of formula (II) were reacted with a support in order to obtain compounds of general formula (IXa) or (IXb) or (XII) hereafter and concomitantly reacted with themselves in order to create covalent bonds contained in formulae (IXc), (IXd), (XIII) or (XIV), hereafter.
The simultaneous employment of a reaction of silane derivatives of polysaccharides with a support and between them allows the creation of a three-dimensional network of silane derivatives bound in a covalent fashion to a support.
The difficulty of representing a support material according to the invention is obvious. Formula (IX) hereafter represents one of the possible variants of the set of formulae (IXa), (IXb), (IXc), (IXd), (XII), (XIII) and (XIV), when m is equal to 1, m being the symbol defined in formula (II).
The reactions employed are the following:
reaction with support of chlorosilanes, hydroxysilanes and alkoxysilanes for the creation of xe2x89xa1Sixe2x80x94Oxe2x80x94 (support) bonds;
creation of siloxane bonds xe2x89xa1Sixe2x80x94Oxe2x80x94Sixe2x89xa1
or disiloxane bonds 
by reacting silane derivatives with each other.
The reaction of chlorosilanes, hydroxysilanes and alkoxysilanes with a support is known per se and was described for example in the work xe2x80x9cChromatographies en phases liquide et supercritiquexe2x80x9d by R. Rosset, M. Caude and A. Jardy, 1991, Masson S. A.
For example, a support of general formula (XI) schematized below: 
and where the formulae below schematize the reactive part of the support 
and a compound containing a radical of general formula (II), and which can, also in order to simplify the presentation of reaction diagrams, be symbolized by a radical of general formula:
(X)3Sixe2x80x94Rxe2x80x94xe2x80x83xe2x80x83(XIa) 
where R represents the radical: 
The employment of the support and compounds (X)3Sixe2x80x94Rxe2x80x94 leads to the following series of reactions: 
The symbol 
of formulae (IX), (IXc) and (IXd) both represents a compound of formula (Ia) to (Ik) and schematizes a chiral osidic unit of an osidic linkage of a silane derivative of a polysaccharide.
The support materials have a complex structure as they are three-dimensional. They can be represented by the set of general formulae (IXaa), (IXa), (IXbb), (IXb), (IXc), (IXd), (XII), (XIII) and (XIV).
The compounds of general formula (IX) represent one of the possible combinations:
reaction with the support leading to compounds of formulae (XII) when m=1;
and concomitant reaction leading to compounds of formula (XIII) when m=1, i.e. formula (IXc),
m having the same meaning as in formula (II).
In reality there are a significant number of possible combinations for the compounds of general formula (IXaa), (IXa), (IXbb), (IXb) and (XII).
The employment of chlorosilanes, hydroxysilanes and alkoxysilanes of polysaccharides on supports leads to compounds of general formula (IX).
The supports used can be silica gel, alumina, zirconia, titanium oxide or magnesium oxide.
Concomitantly to the reactions described previously and resulting in the formation of compounds of general formula (IXaa), (IXa), (IXbb), (IXb) and (XII), a cross-linking reaction occurs between the chains of the silane derivatives of polysaccharides of formulae (Ia) to (Ik). In fact, this reaction takes place simultaneously as the chemical functions employed, chlorosilanes, hydroxysilanes and alkoxysilanes, are strictly identical to those previously employed with the support.
In fact, an interchain cross-linking occurs with the silane derivative of polysaccharide leading to the formation of a three-dimensional network by the creation of bonds:
xe2x89xa1Sixe2x80x94Oxe2x80x94Sixe2x89xa1or 
The principle of the cross-linking by reaction of silanes contained on two different chains of the silane derivative of polysaccharide is schematized in the reaction below: 
where xe2x80x9csupportxe2x80x9d represents a compound of general formula 
with Si representing the silicon or titanium or zirconium or aluminium or magnesium atom;
where W, A, Y and X are as defined previously in formulae (Ia) to (Ik);
and where xe2x80x9cchiral unitxe2x80x9d represents a compound of formula (Ia) to (Ik).
The invention also relates to a method for obtaining support materials which comprises:
physically depositing a silane derivative of polysaccharide of general formula (Ia) to (ik) on a support of general formula: 
where Si has the same meaning as in formula (X):
and reacting the silanes represented in the radical of formula (II) according to two principle reaction methods (a) and (b):
a) reaction with a support of formula (X) to lead to the compounds of general formula (IXaa), (IXa), (IXbb), (IXb), (XII) and (IX);
b) cross-linking said silanes between themselves to lead to compounds of general formula (IXc), (IXd), (XIII) and (XIV).
Formula (IXc) corresponds to formula (XIII) for m=1
Formula (IXd) corresponds to formula (XIV) for m=1, m having the same meaning as in formula (II).
The two reaction methods (a) and (b) are carried out simultaneously and allow the bonding of the silane derivative of polysaccharide by a covalent bond onto the support and polymerizing and cross-linking said silane derivatives of polysaccharides in a three-dimensional network.
Surprisingly, the support materials obtained possess a remarkable stability in all organic solvents, and more particularly in polar organic solvents having a high dissolving power for benzoate and carbamate derivatives of polysaccharides, such as chloroform, acetone, tetrahydrofuran, dioxan or toluene.
Equally surprisingly, these support materials are stable in the solvents mentioned previously up to temperatures of 80xc2x0 C. or more. For example, a test for selectivity (xcex1) carried out on 2,2,2-trifluoro-1(9-anthryl) ethanol with a support material synthesized according to Example 1 showed that the selectivity factor xcex1 (xcex1=1.54 in chloroform) obtained according to Example 1, is not affected by the passage of some 1000 dead column volumes of the following solvents:
These properties permit consideration of the use of support materials in processes for the separation or preparation of enantiomers using any type of polar solvent up to temperatures of at least 80xc2x0 C., which seems particularly attractive for industrial applications.
The stability of the support materials was also evaluated by dissolution at reflux of the various solvents of the preceding table. Surprisingly the results show that the loss of mass of support material synthesized according to Example 1, is nil after hot filtration and drying. This result indicates that the silane derivative of polysaccharide of example 1 is indeed bound to the support by a covalent bond and that the creation of Sixe2x80x94Oxe2x80x94Sixe2x80x94 bonds has occurred between the chains of the silane derivative of polysaccharide, the cross-linking obtained having concerned all of the structure of the sitane derivative of polysaccharide. In fact, the silane derivatives of polysaccharides of formulae (Ia) to (Ik) are soluble in polar organic solvents such as those mentioned in the preceding table, cold and hot. (Furthermore, this property is used to realize the physical deposit of the compounds of formula (Ia) to (Ik) on a support). The loss of mass of the support material being nil, it can be estimated that compounds of the chemical structure represented by formulae (Ia) to (Ik) no longer exist in said support materials, which indicates that the totality of the compounds of formula (Ia) to (Ik) were transformed into support material of general formula (IX).
The physical deposit of a derivative of polysaccharide of general formula (Ia) to (Ik) on a support is realized according to two techniques:
evaporation of a solution of said derivatives of polysaccharides at normal pressure or under vacuum, in the presence of a support; or
precipitation by addition of a solvent in which said derivatives of polysaccharides are insoluble, in the presence of a support.
Generally, said derivatives of polysaccharides are solubilized in polar organic solvents such as chloroform, dichloromethane, acetone, dioxan, pyridine, tetrahydrofuran or toluene. A support of general formula (XI) with a granulometry of 0.1 xcexcm to 1 mm and with a pore diameter of 10 xc3x85 to 10 000 xc3x85 is added to this solution of derivatives of polysaccharides, the preferred support being silica gel.
The quantity of polysaccharide varies from 1 to 70% by weight relative to the mass of support added. A suspension is obtained.
If the technique by evaporation is chosen, the suspension obtained previously is dried by distillation of the solvent at normal pressure or under vacuum. A product is obtained which is constituted by a support on which a silane derivative of polysaccharide of formula (Ia) to (Ik) is physically deposited. This product is called composite.
If the technique by precipitation is chosen, a solvent in which the derivative of polysaccharide is insoluble is added to the suspension obtained previously, hexane or heptane being the preferred solvents. The suspension is filtered, washed with heptane and dried at 40xc2x0 C. under vacuum. A product is obtained of the same nature as that obtained in the technique by evaporation. This product is also called composite.
The composite thus obtained is suspended in a solvent in which the derivative of polysaccharide is insoluble, the preferred solvents being heptane or hexane, and the suspension is taken to reflux for, for example, twelve hours. The supply of calories allows the chlorosilanes, hydroxysilanes and alkoxysilanes contained in the silane derivatives of polysaccharides, to enter into reaction with the silanol groups contained in the surface of the silica gel support. The grafting reaction of the chlorosilanes, hydroxysilanes and alkoxysilanes on the silica gel supports containing silanols is known per se and was described in several works such as xe2x80x9cSilica Gel and Bonded Phasesxe2x80x9d, R. P. W. Scott, 1993, Separation Science Series, R. P. W. Scott and C. F. Simpson editors, John Wiley and Sons Ltd. The use of chlorosilanes leads to the formation of hydrochloric acid and trapping this takes place by the use of a base such as pyridine. The use of hydroxysilane leads to the formation of water. The use of alkoxysilanes leads to the formation of the corresponding alcohols (methanol for methoxysilane and ethanol for ethoxysilane). These different grafting reactions lead to the formation of a chemical covalent bond with the support of the same chemical nature [xe2x80x94Sixe2x80x94Oxe2x80x94(Support)].
The polymerization of chlorosilanes, hydroxysilanes and alkoxysilanes is known per se and was described in xe2x80x9cSilica Gel and Bonded Phasesxe2x80x9d, R. P. W. Scott, 1993, Separation Science Series, R. P. W. Scott and C. F. Simpson editors, John Wiley and Sons Ltd.
The polymerization of chlorosilanes takes place in the presence of traces of water, hydroxysilanes polymerize by forming water and alkoxysilanes polymerize by releasing the corresponding alcohol (methanol for methoxysilanes and ethanol for ethoxysilanes). These different polymerization reactions lead to the realization of covalent bonds of the same chemical nature: Sixe2x80x94Oxe2x80x94Si (the siloxane bond or siloxane graft). By only taking into account, at the level of the composite, the reactive chemical parts, namely the support and the radical of formula (II) contained in the derivatives of polysaccharides (Ia) to (Ik), the balance of the two concomitant chemical reactions employed to synthesize the support material from the composite is the following:
reaction with the support 
In order to avoid too great a complexity in the figure representing the support material of general formula (IX), the radical part [CH2xe2x80x94CH2xe2x80x94Wxe2x80x94Si(X)3]m-1 is not shown, it having not reacted.
Although not represented in formula (IX), the radical part above can obviously enter into the reaction and particularly in the reaction concomitant to the previous reaction xe2x80x9creaction with the supportxe2x80x9d and which is called xe2x80x9ccross-linkingxe2x80x9d. In this case the radical part m-1 is involved and leads to a reaction product of order m-2 and so on.
Cross-linking: 
In formulae (XIII) and (XIV), as in the case of the compounds of formulae (XII), the radical part [xe2x80x94CH2xe2x80x94CH2xe2x80x94Wxe2x80x94Si(X)3]m-1 can concomitantly react in order to lead to a new covalent bond of order m-2, which can itself lead to a bond of order m-3 and so on.
The invention also relates to methods for using said support materials in separation or in preparation of enantiomers by employing in:
gas chromatography
liquid chromatography, from xe2x88x9210xc2x0 C. to +80xc2x0 C., in particular in pure polar organic solvents such as those mentioned in the table below:
In hydro-organic, aqueous or organic mixtures, under isocratic conditions or in gradient mode:
supercritical chromatography
electrophoresis or electrochromatography
percolation through membranes constituted by said support materials
organic synthesis in heterogeneous medium.
The following examples illustrate the present invention but in no way limit it.